The principal objective of the proposed research program is to achieve a better understanding of hemoglobin synthesis in sickle cell disorders, thalassemia syndromes and other hemoglobinopathies. The diversity of expression of thalassemia will be investigated in alpha-thalassemia, beta-thalassemia, delta beta-thalassemia, hereditary persistence of fetal hemoglobin, sickling disorders and alpha-chain variants. Newer techniques of molecular biology, in addition to hematologic genetic and radiochemical methods of study, will be involved, including the use of mRNA and DNA from thalasessmia disorders and normal persons in hybridization experiments and recombinant DNA studies. The long-range objectives of these studies is to provide information for accurate genetic counselling and for treatment of human hemoglobinopathies and to gain better understanding of the control mechanisms of protein synthesis in mammalian cells.